Phosphonamido thiazoles and their utility as insecticides

ABSTRACT

IN WHICH R is alkyl; R1 is alkyl, alkenyl, alkynyl, benzyl, cyanoalkyl or alkylthio-alkylene; R3 is hydrogen or alkyl; R4 is hydrogen, alkyl or alkylthioalkylene are used as insecticides and acaricides.   Compounds of the formula

United States Patent [1 1 Fancher I Oct. 9, 1973 PHOSPHONAMIDO Tl-IIAZOLES AND THEIR UTILITY AS INSECTICIDES Primary Examiner-Albert T. Meyers Assistant ExaminerD. W. Robinson [75] Inventor. glaelvivfellyn W. Fancher, Onnda, Att0mey Danie1 C. Block et a1.

[73] Assignee: Stauffer Chemical Company, New [57] ABSTRACT York Compounds of the formula [22] Filed: Dec. 11,1972

e e Ii [2]] Appl. No.. 313,702 \I L l Related US. Application Data S [62] E 3 5 2? 198912 1971 in which R is alkyl; R is alkyl, alkenyl, alkynyl, benzyl, cyanoalkyl or alkylthio-alkylene; R is hydrogen or [52] US. Cl 424/200. alkyl; R is hydrogen, alkyl or alkylthioalkylene are [51] m. C. i"'"111'?"11'111'i117"'1111""'i11'1';;01.. 9/36 eeee ee eeeeeeieieee eee eeeeieieee- [58] Field of Search 424/200 35 Claims, No Drawings PHOSPHONAMIDO THIAZOLES AND THEIR UTILITY AS INSECTICIDES This is a continuation, division, of application Ser. No. 198,012, filed Oct. 29, 1971, now US. Pat. No. 3,723,450.

This invention relates to certain novel phosphoruscontaining chemical compounds and their use as insecticides and acaricides. More particularly, the compounds are certain substituted 2-N-phosphonamido thiazoles.

The compounds of this invention that are useful as insecticides and acaricides are those having the formula in which R is alkyl having one to four carbon atoms, inclusive; R is alkyl having one to eight carbon atoms, inclusive, alkenyl having three to six carbon atoms, inclusive, preferably three carbon atoms, alkynyl having three to six carbon atoms, inclusive, preferably three carbon atoms, benzyl, cyano alkyl in which the alkyl group has one to four carbon atoms, inclusive, preferably one carbon atom, alkylthioalkylene having a total of two to six carbon atoms, preferably two carbon atoms; R is hydrogen or alkyl having one to four carbon atoms, inclusive, preferably methyl; and R is hydrogen, alkyl having one to four carbon atoms, inclusive, preferably methyl, or alkylthioalkylene having a total of from two to six carbon atoms, inclusive.

The compounds having the formula in which R, R,, R R and R are as defined above can be prepared by the following reactions:

X represents a halogen such as chlorine, bromine or iodine.

The compounds of the instant invention can be prepared by the reactions depicted in the above equations. Selection of time, temperature and solvents can be made within wide limitations. Once the equations and reactants are known, the specific procedures can be varied and modified to accommodate and facilitate the reaction. The intermediate from equation (a), i.e., the phosphonamide salt, can be isolated or reacted in the same or different solvent, or the reaction can be carried through to completion without isolation.

To facilitate reaction (a), a non-reactive acid acceptor isused as a catalyst. In the following specific examples, triethylamine is used as the base, however, other non-reactive acid acceptors would be acceptable. Similarly, in reaction (b), it was found that the reaction can be promoted by a slightly basic medium. This can be accomplished by adding triethylamine as required.

The compounds of the present invention and their preparation are more particularly illustrated by the following examples. Following the examples is a table of compounds which are prepared according to the procedures described herein.

EXAMPLE I Preparation of Z-(S-methyl ethyl phosphonamidodithioyl)-thiazole. Seven and four-tenths grams (7.4 g., 0.03 mole) of ethylthionophosphine sulfide was slurried in ml. of dry dioxane and to this mixture was added 7.0 grams (0.07 mole) of 2-aminothiazole at 25C. The temperature was allowed to increase to 30. A white solid precipitated. The mixture was stirred and warmed at 4548 for 0.5 hours, cooled to 15 and 6.1 g. (0.06 mole) (8.4 ml.) of triethylamine was added followed by 9.9 g. (0.07 mole) (4.4 ml.) of methyl iodide. The mixture was stirred and warmed at 42-48 for 1.5 hours. The dioxane was removed on a rotary evaporator and the residue dissolved in benzene and washed twice with dilute sodium chloride solution. The benzene solution, containing the product, was dried over anhydrous magnesium sulfate, filtered and the solvent removed on a rotary evaporator. There was obtained 15.1 g. of the title compound, a viscous liquid, n 1.6570.

EXAMPLE II Preparation of the Intermediate 2-(S-triethylammonium-ethyl phosphonamidodithioyl)-thiazole. Forty grams (40 g., 0.4 mole) of 2- aminothiazole was slurried in 200 ml. of benzene. To this slurry was added 81 g. (0.8 mole) (111 ml.) of triethylamine, followed by 52.1 g. (0.21 mole) of ethylthionophosphine sulfide with stirring. The temperature rose from 24 to 60C. Stirring at ambient temperature was continued for 4 hours. The crystalline solid was filtered off and washed with diethyl ether and n-hexanef The product was filtered to remove the bulk of the solvent. The triethylamine salt still contained some solvent and weighed 140.1 g., m.p. 98l04C. This intermediate was used directly in the next step. Preparation of 2-(S-n-buty1, ethyl pohsphonamidodithioyl)- thiazole. Thirteen grams (13 g., 0.04 mole) of the triethylamine salt, supra, was mixed with 30 ml. of dimethyl formamide and 7.4 g. (0.04 mole) of n-butyl iodide was added. The mixture was tested and found to be slightly basic. The mixture was stirred at 55-60C. for 3 hours, then poured into water and extracted with benzene. The benzene phase was washed with water,

dried over anhydrous magnesium sulfate, filtered, and evaporated on a rotary evaporator. There was obtained 10.0 g. (81.3 percent of theory) of the title compound, n 1.5932.

The following is a table of certain selected compounds that are preparable according to the procedure described herein. Compound numbers are assigned to each compound and are used throughout the remainallowed to dry. The aliquots were there to achieve desired toxicant concentration ranging from 100 ug/per Petri dish to that at which 50 percent mortality was attained. The Petri dishes were placed in a circular cardder of the application. 5 board cage, closed on the bottom with cellophane and TABLE I s N R; l! fi' f-ii E R 121s H s 4 Compound .\I.P., C. number R1 R3 R4 or m)" CH; H H 1.6570 C2115 H H 1 6262 CH; H H 92-95 CzHs H H 1. 6367 n-C H: H H 1. 6199 l-C3H7 H H 1. e052 CHz=CHCHz H H 1.6496 CH CCH: H H 1.6414 CH3(CH:)1 H H 1. 5564 CQHS H H 1 6343 11 CzH (CH3):CHCH2CH1 H H 1.5436 12 CzHr (CH3)2CHCH2 H H 1.5613

13 C-1H5 (3H3 H 11 1.5507

CHKCHQACH 14 C2H5 (3H3 H H 1. 6010 CHJCHQCH CH3(CH2)$ H H 1. 5932 (CzHs)2CHCH2 nC4H H H 1. 6037 NCCHI H H 1. 5390 CHQSCH: H H 1. 6516 CH3 CH3 H 1. 6544 CH2CH=CH2 CH: H 1. 6303 CHzCz C CH: H 1. 6446 CH3 CzlhSCH: H 1. 6395 CH; CHaSCHz H 1.6608 CQHS CHrSCIL H 1. 6327 Other examples of compounds falling within the gecovered on top with cloth netting. Twenty-five female neric formula presented herein, which are preparable houseflies, three to five days old, were introduced into by the aforedescribed procedures and which may be the cage and the per cent mortality was recorded after formulated into insecticidal and acaricidal composi- 48 hours. Th;e l. .D 5( values are expressed irfirms of tions and applied as herein illustrated are: pg. per 25 female flies. The results of this insecticidal evaluation test are given in Table II under HF. R R R R C,H CH, Ci-l, CH; In the lygus bug (LG) Lygus hesperus test, 10 to 25 CH CH CH CH JL CHZSCH: 2 weeic old nymphs of lygus bug were placed in sepa (5H, eu ectic H, rate circular cardboard cages sealed on one end With cellophane and covered by a cloth netting on the other. INSECTICIDAL EVALUATION TESTS Aliquots of the toxicants, dissolved in an appropriate The term "insect is used herein in its broad common solvent, were diluted in water containing 0.002 percent usage to include spiders, mites, ticks and like pests of a wetting agent, Sponto 221 (polyoxyether of alkylwhich are not in the strict biological sense classified as ated phenols blended with organic sulfonates). Test insects. The term insectl is used to refer not only to concentrations ranged from 0.05 percent downward to those small invertebrate animals belonging mostly to that at which 50 percent mortality was obtained. Each the class lnsecta, comprising six-legged usually winged of the aqueous suspensions of the candidate comforms, as beetles, bugs, bees, flies, and so forth, but also pounds were sprayed onto the insect through the cloth to other allied classes of arthropods whose members netting by means of a hand-spray gun. Per cent mortalare Wingless and usually have more than six legs, as spiity in eaclrcase recorded after 24 and 72 hours CQlLIlt S ders, mites, ticks, centipedes, and wood lice. were made to determine living and dead insects. The The following insect species were used in evaluation LD-SO values expressed as per cent of toxicant in the tests for insecticidal activity: aqueous spray were calculated and recorded. These 1. Housefly (HF) Musca domestica (Linn.) values are reported under the column LB" in Table II. 2. Lygus Bug (LB) Lygus hesperus (Knight) The insect species black bean aphid (BA) Aphisfabae 3. Bean Aphid (BA) Aphis fabae (Scop.) v (Scop.) was also employed in the test for insecticidal The housefly (HF) was used in evaluation tests of sei y Young nastlll'tium (Tropaevlum PJ Plants, P- lected compounds as insecticides by the following proproximately 2 I0 3 inches tall, were used as the 1105! cedure. A stock solution containing pig/ml. of the toxicant in an appropriate solvent was prepared. Aliquots of this solution were combined with l milliliter of an acetone-peanut oil solution in a glass Petri dish and plants for the bean aphid. The host plant was infested with approximately 50-75 of the aphids. The test chemical was dissolved in acetone, added to water which contained a small amount of Sponto 221, an

emulsifying agent. The solution was applied as a spray to the infested plants. Concentrations ranged from 0.05 per cent downward until an LD-50 value was achieved. These results are given in Table II under the column BA".

ACARICIDAL EVALUATION TEST The two-spotted mite (28M), Tetranychus urlicae (Koch), was employed in tests for miticides. Young pinto bean plants or lima bean plants (Phaseolus sp.) in the primary leaf stage were used as the host plants. The young pinto bean plants were infested with about 100 mites of various ages. Dispersions of candidate materials were prepared by dissolving 0.1 gram in ml. of a suitable solvent, usually acetone. Aliquots of the toxicant solutions were suspended in water containing 0.002 percent v/v Sponto 221, polyoxyethylene ether sorbitan monolaurate, an emulsifying agent, the amount of water being sufficient to give concentrations of active ingredient ranging from 0.05 percent to that at which 50 percent mortality was obtained. The test suspensions were then sprayed on the infested plants to the point of run off. After 7 days, mortalities of the post-embryonic form was determined. The percentage of kill was determined by comparison with control plants which had not been sprayed with candidate compounds. The LD- 50 value was calculated using wellknown procedures. These values are reported under the columns ZSM-PE and 2SM-Eggs, in Table II.

SYSTEMIC EVALUATION TEST This test evaluates the root absorption and upward translocation of the candidate systemic compound. The bean aphid (BA) Aphis fabae (Scop.) and two-spotted mite (28M) Tezranychus urticae (Koch), were employed in the test for systemic activity.

Young nasturtium (Tropaeolum sp.) plants were used as the host plants for the bean aphid. The host plants, 2-3 inches tall, were transplanted into one pound of soil that had been treated with the candidate compound. Immediately after planting in the treated soil, the plants were infested with 50-75 aphids of various ages. Concentrations of toxicant in the soil ranged from 10 ppm per pound of soil downward until an LD-50 value was obtained. Mortality was recorded after 72 hours.

The percentage of kill of the test species was determined by comparison with control plants placed in distilled water or untreated soil. The LD-50 values were calculated. These systemic test results are reported in Table II under the column BA-Sys."

Aliquots of the toxicant dissolved in an appropriate solvent are diluted in water and placed in glass bottles. Pinto bean plants (Phaseolus sp.) with expanded primary leaves were placed in the solutions so that the roots and major portion of the stem were completely immersed. Immediately after placement of the plants, the leaves were infested with 75-100 mites of various ages. Total mortality of adults, nymphs and eggs were recorded after 1 week. The LD-50 values expressed in ppm of toxicant in the aqueous suspensions are reported in Table II under the column 2SM-Sys."

TABLE IL-(LD- VALUES) HF, Percent BA- 2 SM, percent 2 SM- Compound 4 Sys. Sys. number 25+ LB BA p.p.m. PE Eggs p.p.m

N OTE. indicates not tested for the indicated insect species.

As those in the art are well aware, various techniques are available for incorporating the active component or toxicant in suitable pesticidal compositions. Thus, the pesticidal compositions can be conveniently prepared in the form of liquids or solids, the latter preferably as homogeneous free-flowing dusts commonly formulated by admixing the active component with finely divided solids or carriers as exemplified by talc, natural clays, diatomaceous earth, various flours such as walnut shell, wheat, soya bean, cottonseed and so forth.

Liquid compositions are also useful and normally comprise a dispersion of the toxicant in a liquid media although it may beconvenient to dissolve the toxicant directly in a solvent such as kerosene, fuel oil, xylene, alkylated naphthalenes or the like and use such organic solutions directly. However, the more common procedures is to employ dispersions of the toxicant in an aqueous medium and such compositions may be produced by forming a concentrated solution of the toxicant in a suitable organic solvent followed by dispersion in water, usually with the aid of surface active agents. The latter, which may anionic, cationic or nonionic types, are exemplified by sodium stearate, potassium oleate and other alkaline metal soaps and detergents such as sodium lauryl sulfate, sodium naphthalene sulfonate, sodium alkyl naphthalene sulfonate, methyl cellulose, fatty alcohol ethers, polyglycol fatty acid esters, and other polyoxyethylene surface active agents. The proportion of these agents commonly comprises 1-15 percent by weight of the pesticidal compositions although the proportion is not critical and may be varied to suit any particular situation.

What is claimed is:

l. The method of killing pests selected from the group consisting of insects and acarides comprising ap plying a pesticidally effective amount to the said pest or pest habitat of a compoqnd having the formula in which R is alkyl having one to four carbon atoms, inclusive; R is alkyl having one to eight carbon atoms, inclusive, alkenyl having three to six carbon atoms, inclusive, benzyl, cyano alkyl in which the alkyl group has one to four carbon atoms, inclusive, or alkylthioalkylene having a total of two to six carbon atoms; R, is hydrogen or alkyl having one to four carbon atoms, inclusive; and R, is hydrogen, alkyl having one to four carbon atoms, inclusive, or alkylthioalkylene having a total of from two to six carbon atoms, inclusive.

2. A method according to claim 1 in which R is alkyl, R,-is alkyl, R, is hydrogen and R, is hydrogen.

3. The method according to claim 2 in which R is ethyl and R, is methyl.

4. The method according to claim 2 in which R is ethyl and R, is ethyl.

5. The method according to claim 2 in which R is methyl and R, is methyl.

6. The method according to claim 2 in which R is methyl and R, is ethyl.

7. The method according to claim 2 in which R is ethyl and R, is n-propyl.

8. The method according to claim 2 in which R is ethyl and R, is isopropyl.

9. The method according to claim 2 in which R is ethyl and R, is n-octyl.

10. The method according to claim 2 in which R is ethyl and R, is 3-methylbutyl.

11. The method according to claim 2 in which R is ethyl and R, is isobutyl.

12. The method according to claim 2 in which R is ethyl and R, is l-methylheptyl.

13. The method according to claim 2 in which R is ethyl and R, is n-hexyl.

14. The method according to claim 2 in which R is ethyl and R, is Z-ethylbutyl.

15. The method according to claim 2 in which R is ethyl and R, is n-butyl.

16. A method according to claim 1 in which R is alkyl, R, is benzyl, R, is hydrogen, and R, is hydrogen.

17. The method according to claim 16 in which R is ethyl.

18. A method according to claim 1 in which R is al- 8 kyl, R, is alkenyl, R, is hydrogen, and R, is hydrogen.

19. The method according to claim 18 in which R is ethyl and R, is 2-propenyl.

20. A method according to claim 1 in which R is alkyl, R, is alkynyl; R, is hydrogen; and R, is hydrogen.

21. The method according to claim 20 in which R is ethyl and R, is 2-propynyl.

22. A method according to claim 1 in which R is alkyl, R, is cyanoalkyl, R, is hydrogen and R, is hydrogen.

23. The method according to claim 22 in which R is ethyl, and R, is cyanomethyl.

24. A method according to claim 1 in which R is alkyl, R, is alkylene, R, is hydrogen and R, is hydrogen.

25. The method according to claim 24 in which R is ethyl and R, is methylthiomethylene.

26. A method according to claim 1 in which R is alkyl, R, is alkyl, R, is alkyl and R, is hydrogen.

27. The method according to claim 26 in which R is ethyl, R, is methyl and R, is methyl.

28. A method according to claim 1 in which R is alkyl, R, is alkenyl, R, is alkyl and R, is hydrogen.

29. The method according to claim 28 in which R is ethyl, R, is Z-propenyl and R, is methyl.

30. A method according to claim 1 in which R is alkyl, R, is alkynyl, R, is alkyl and R, is hydrogen.

31. The method according to claim 30 in which R is ethyl, R, is 2-propynyl and R, is methyl.

32. A method according to claim 1 in which R is alkyl, R, is alkyl, R, is alkylthioalkylene and R, is hydrogen.

33. The method according to claim 32 in which R is ethyl, R, is methyl and R, is ethylthiomethylene.

34. The method according to claim 32 in which R is ethyl, R, is methyl and R, is methylthiomethylene.

35. The method according to claim 32 in which R is ethyl, R, is ethyl and R, is methylthiomethylene. 

2. A method according to claim 1 in which R is alkyl, R1 is alkyl, R3 is hydrogen and R4 is hydrogen.
 3. The method according to claim 2 in which R is ethyl and R1 is methyl.
 4. The method according to claim 2 in which R is ethyl and R1 is ethyl.
 5. The method according to claim 2 in which R is methyl and R1 is methyl.
 6. The method according to claim 2 in which R is methyl and R1 is ethyl.
 7. The method according to claim 2 in which R is ethyl and R1 is n-propyl.
 8. The method according to claim 2 in which R is ethyl and R1 is isopropyl.
 9. The method according to claim 2 in which R is ethyl and R1 is n-octyl.
 10. The method according to claim 2 in which R is ethyl and R1 is 3-methylbutyl.
 11. The method according to claim 2 in which R is ethyl and R1 is isobutyl.
 12. The method according to claim 2 in which R is ethyl and R1 is 1-methylheptyl.
 13. The method according to claim 2 in which R is ethyl and R1 is n-hexyl.
 14. The method according to claim 2 in which R is ethyl and R1 is 2-ethylbutyl.
 15. The method according to claim 2 in which R is ethyl and R1 is n-butyl.
 16. A method according to claim 1 in which R is alkyl, R1 is benzyl, R3 is hydrogen, and R4 is hydrogen.
 17. The method according to claim 16 in which R is ethyl.
 18. A method according to claim 1 in which R is alkyl, R1 is alkenyl, R3 is hydrogen, and R4 is hydrogen.
 19. The method according to claim 18 in which R is ethyl and R1 is 2-propenyl.
 20. A method according to claim 1 in which R is alkyl, R1 is alkynyl; R3 is hydrogen; and R4 is hydrogen.
 21. The method according to claim 20 in which R is ethyl and R1 is 2-propynyl.
 22. A method according to claim 1 in which R is alkyl, R1 is cyanoalkyl, R3 is hydrogen and R4 is hydrogen.
 23. The method according to claim 22 in which R is ethyl, and R1 is cyanomethyl.
 24. A method according to claim 1 in which R is alkyl, R1 is alkylene, R3 is hydrogen and R4 is hydrogen.
 25. The method according to claim 24 in which R is ethyl and R1 is methylthiomethylene.
 26. A method according to claim 1 in which R is alkyl, R1 is alkyl, R3 is alkyl and R4 is hydrogen.
 27. The method according to claim 26 in which R is ethyl, R1 is methyl and R3 is methyl.
 28. A method according to claim 1 in which R is alkyl, R1 is alkenyl, R3 is alkyl and R4 is hydrogen.
 29. The method according to claim 28 in which R is ethyl, R1 is 2-propenyl and R3 is methyl.
 30. A method according to claim 1 in which R is alkyl, R1 is alkynyl, R3 is alkyl and R4 is hydrogen.
 31. The method according to claim 30 in which R is ethyl, R1 is 2-propynyl and R3 is methyl.
 32. A method according to claim 1 in which R is alkyl, R1 is alkyl, R3 is alkylthioalkylene and R4 is hydrogen.
 33. The method according to claim 32 in which R is ethyl, R1 is methyl and R3 is ethylthiomethylene.
 34. The method according to claim 32 in which R is ethyl, R1 is methyl and R3 is methylthiomethylene.
 35. The method according to claim 32 in which R is ethyl, R1 is ethyl and R3 is methylthiomethylene. 